Gene Cluster Directs Diversified Carbazole Biosynthesis via Cooperative Halogenation, Hydroxylation, and Methylation
Qiaoling Wu1, Feng Li1, Ming Peng1
1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese, Key Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.
Abstract:
Chlocarbazomycins are bioactive carbazoles with therapeutic potential. Here, we report a conserved gene cluster (ccz) that directs its biosynthesis via a novel pathway. This cluster encodes a versatile tailoring system, including a regioselective halogenase (CczH), dedicated hydroxylases (CczA/J/D), and a bifunctional methyltransferase (CczI) that iteratively methylates and accelerates N-OH dehydroxylation. Our findings provide new enzymes for carbazole pathway engineering and structural diversification.
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